The objectives of this proposal are to examine the hypothesis that refractory disease is distinct from nonrefractory periodontal disease and to identify one or more well-defined syndromes within the refractory subjects based on analysis of microbial and host factors. The specific aims are: 1) identify the predominant bacteria in refractory subjects including unrecognized and uncultivated species using 16S rRNA gene sequences. Analyzing 16S rDNA genes cloned from plaque libraries. Identify the uncultivated oral species and determine their role in periodontal disease. 2) Test the hypothesis that subjects with refractory disease can be distinguished from subjects with treatable periodontitis and periodontal health based upon microbial composition. Twenty-eight sites in 40 subjects in each of 3 groups will be analyzed for levels of 60 cultivable taxa and 120 uncultivated taxa using checkerboard hybridization assays. Allow identification of species that are useful for distinguishing between refractory and treatable periodontitis and health. 3) Test the hypothesis that subjects with refractory disease(s) can be distinguished from those with treatable disease and health based upon host factors such as, genotypes, allotypes, serum IgG2 levels and specific antibodies levels to 40 specific periodontal bacteria. 4) Identify more than 1 disease syndromes within the refractory group based upon microbial and host markers.